Many environmental chemicals are mutagens and potential carcinogens that may inflict heritable genetic damage. There already exist some 70,000 synthetic chemicals in commercial use, with another 1,000 new ones synthesized each year. Thus, the need for effective mutagen screening is clear. A recent National Academy of Sciences (NAS) report, commissioned by the Environmental Protection Agency, underscores this need and the limitations of currently available mutagenicity assays. See Summary and Conclusions, In: Identifying and Estimating the Genetic Impact of Chemical Mutagens, (Ed N. Grossblatt.), National Academy Press, Washington, D.C. pp. 1-138, (1983). The Salmonella/Microsome test developed by Ames and his co-workers is the most widely used assay to identify such compounds, and it detects about 90% of carcinogens examined. Possible reasons for obtaining false negatives and false positives have been considered in the literature. To complement the bacterial tests, several mutagenicity assays utilizing cultured mammalian cells have been developed. These have been useful in identifying several mutagens that the bacterial test fails to detect and they provide a basis for comparing the potential mutagenicity of different agents in eukaryotic cells.
One shortcoming of the mammalian cell assays in use is that, unlike the Ames test, none can determine the type of mutation a mutagen produces. Most of what is known about the types of mutations induced by mutagens is derived from bacterial test systems, and what little understanding we have of the effects of mutagens on the DNA of mammalian cells is often based on extrapolation. Confirmation of such information is frequently circuitous and difficult to obtain. Unfortunately, an argument that a mutagen acts in mammalian cells by inducing frameshifts or transitions is most often by extrapolation from its effects on bacterial cells. The need for more rigorous assessment of the kinds of damage that environmental mutagens can inflict upon mammalian DNA is emphasized by the NAS report. As noted in an editorial in Chemicals and Genetic Damage, Nature, 301:653 (1983), the ideal would be that there should be such a full understanding of what happens metabolically to particular chemicals in mammalian cells such as germ and somatic cells, and such a full catalog of possible interactions with nuclear DNA, that the prediction of mutagenicity would be possible.